The present invention relates to rate-modulated cardiac therapy devices, and, more particularly, to temperature-based, rate-modulated cardiac therapy devices.
Rate-modulated pacemakers, also known as rate-responsive or rate-adaptive pacemakers, stimulate cardiac activity, generally on demand, at a rate determined at least in part by a sensed physiological parameter indicative of required cardiac output. A healthy heart responds to exercise and stress by increasing cardiac output through increased heart rate and stroke volume, and rate-modulated pacemakers more closely approximate this natural response by automatically varying heart rate to meet metabolic demand. Such pacemakers represent a significant advance over early pacemakers, which paced the heart at a single, constant rate, typically near 70 beats per minute. Some patients dependent on fixed-rate pacemakers exhibit limited exercise tolerance because the natural increase in heart rate associated with exercise is not present. While the myocardium is sometimes healthy enough to increase cardiac output by increasing stroke volume, not all patients have adequate response with stroke volume increases alone. Increasing the pacing rate during exercise significantly increases cardiac output and, consequently, exercise tolerance.
Because of its potential in cardiac care, rate modulation is the subject of extensive, ongoing research. A number of biologic parameters have been proposed as indicators of the onset and degree of exercise, including venous pH, Q-T interval, respiratory rate, body motion, stroke volume, venous oxygen saturation, evoked electrogram analysis, pre-ejection period, pressure, and temperature. A review of the clinical experience and basic research in this area is found in Fearnot et al., "A Review of Pacemakers that Physiologically Increase Rate: The DDD and Rate-Responsive Pacemakers," Progress in Cardiovascular Diseases 29(2):145-164, 1986. Each proposed parameter has both advantages and disadvantages for control of pacing rate. Problems with sensitivity, accuracy, and transducer reliability and power consumption impede the practical implementation of some of these techniques. Moreover, optimal pacemaker response is difficult to attain because physiological parameters which vary in response to exercise and stress often exhibit similar variations in response to other conditions not affecting cardiac output requirements. Blood temperature, for example, is affected by factors other than metabolic activity, such as environmental ambient temperatures encountered during swimming, bathing and other activities, the temperature of ingested food and drink, changes in posture, and fever. Algorithms capable of differentiating between certain true and false indications of exercise are difficult to design because responses to many conditions vary widely from patient to patient. Furthermore, algorithm efficacy is difficult to verify, particularly in human tests, and an algorithm designed to solve one problem may actually introduce others.
It has long been known on a qualitative level that a relationship exists between some body temperatures and heart rate, but it was not until the mid-1970s that attempts were made to modify pacemaker pulse generator circuitry to respond in even a primitive fashion to temperature. Only in this decade has quantitative analysis of the temperature-rate relationship been performed in an effort to derive and implement accurate rate-control algorithms for a temperature-based, rate-modulated pacemaker.
An early attempt to respond to temperature, described in Fischell U.S. Pat. No. 3,867,950, involved measurement of body temperature. The pulse generating circuitry in the pacemaker was designed such that the output pulse rate would vary as a function of battery voltage and also as a function of body temperature as measured at the pacemaker case. A capacitor having a high temperature coefficient was used for temperature sensing, and the pacemaker's response to temperature was a fixed response corresponding to the temperature characteristics of the capacitor.
In German patent application No. 2609365, Csapo suggested the alternative use of either central body temperature or central blood temperature as a suitable parameter for the control of heart rate. The application discloses a temperature sensor lodged in the heart and connected as a base resistor in a blocking oscillator of the pulse generator to control the oscillator frequency and thereby the heart rate as a fixed function of instantaneous temperature. As with the Fischell pacemaker, variations in pacing rate with the proposed Csapo pacemaker would be solely dependent on the temperature characteristic of a selected hardware component, in this case a selected thermistor or other temperature sensor serving as the base resistor. Changes in central blood temperature during exercise were also the subject of a study reported by Csapo et al. in an article entitled "Auto-Regulation of Pacemaker Rate by Blood Temperature," presented at the VIII World Congress of Cardiology in Tokyo Japan, Sept. 17-23, 1978. Csapo et al. suggested in this article that the central blood temperature should regulate the heart rate along an S-curve, and the article includes a graph of an S-curve relationship between heart rate and temperature and also an equation, HR=81+21 tang (2X-71.2).
In Cook et al. U.S. Pat. Nos. 4,436,092 and 4,543,954, defined specific algorithms for a temperature-based exercise-responsive cardiac pacemaker. An important teaching of these patents is that the rate of change of temperature, as opposed to the instantaneous temperature, can be used as an indicator of exercise. Another important teaching is that cardiac rate may be calculated as a combination of rate components which individually vary in response to temperature conditions. In the preferred embodiments of the inventions described in these patents, venous blood temperature in the right ventricle of the heart is measured and processed according to an algorithm which represents the mathematical function between right ventricular blood temperature and heart rate in a normally functioning heart.
It is now known that two major mechanisms related to metabolic activity produce significant changes in blood temperature. The first is an increase in blood temperature due to increased metabolism and therefore heat generation during physical activity or emotional stress. The rate of rise is partly dependent upon workload. When the increased metabolism ceases, temperature returns to resting levels. The second mechanism producing a significant change in blood temperature is the response to the onset of activity or anticipation thereof resulting in an abrupt decrease in temperature. This is due to vasoactivity and blood flow redistribution to the cooler peripheral skeletal muscles and skin. An algorithm responsive to the initial drop in temperature was reported by Sellers et al. in the March-April, 1985 edition of Pace magazine, in a poster abstract entitled "Central Venous Temperature Profiles for a Pacemaker Algorithm." Subsequently, another algorithm responsive to the initial drop in temperature was disclosed in Alt et al. U.S. Pat. No. 4,719,920. The algorithm in the Alt et al. pacemaker appears to recognize an exercise-induced temperature dip on the basis of the current operating state of the pacemaker and three threshold-based criteria.
The blood temperature response caused by the above-mentioned major mechanisms may be separated into several components to produce a normal heart rate response. One component is the baseline resting temperature (T.sub.0) which is the temperature of the patient at rest. Resting temperature varies with time of day, baseline metabolic state, and thermoregulatory balance. Another component is the temperature change with respect to the baseline temperature (.DELTA.T), which increases as activity continues and current temperature rises. A third component is the rate of temperature change (dT/dt or (.DELTA.T/.DELTA.t), i.e., the temperature change in a given interval, whether a fixed time interval or some other interval such as a cardiac cycle. Positive values of this component have been shown to be related to work load and oxygen uptake under certain conditions. Certain combinations of particular temperature-based rate components are disclosed in the aforementioned Cook et al. patents and combinations of similar components are incorporated into commercially available pacemakers such as the Kelvin.RTM. 500 pacemaker available from Cook Pacemaker Corporation of Leechburg, Penn.
The Kelvin.RTM. 500 uses the rate of change of temperature, either alone or in conjunction with relative temperature rise above a moving baseline, to identify exercise. The baseline represents resting temperature and is calculated as the second minimum sample of eight temperature samples equally spaced in time, preferably over approximately a two-hour period. When the algorithm determines a significant change from baseline, representing exercise onset, pacing rate is adjusted starting from a programmable base rate. Temperature decrease at the onset of exercise causes pacing rate to increase gradually to a programmed intermediate rate which is maintained for a programmed period of from 2 to 10 minutes. When temperature starts to increase, confirming exercise, the pacemaker algorithm overrides the intermediate rate and gradually increases rate to a programmed upper rate. The algorithm can independently increase heart rate based solely on the rise in temperature if no drop occurs, or based solely on the drop in temperature if no rise occurs, or combinations thereof. The sensitivity of the algorithm to temperature changes and to the rate of rise or fall of temperature is programmable. The algorithm detects the decrease in temperature after peak exercise and decreases heart rate gradually to a programmed lower rate. Pacing rate is changed by incrementing or decrementing the R-to-R interval in steps of 20, 40 or 60 milliseconds, with the ability to further adjust the rate of pacing rate changes by programming either 5 or 10 seconds as the time interval between the step changes in pacing rate. Positive and negative rates of change of temperature are separately compared against a threshold value to determine the presence or absence of an exercise state. In the case of a positive rate of change of temperature, a value proportional thereto is added to a value proportional to the temperature rise above baseline, and pacing rate is incremented if the sum exceeds the threshold. In the case of a negative rate of change of temperature, a value proportional thereto (by a different scale factor than for the positive rate of change) is compared directly to the threshold.
Threshold detection is also the manner in which the initial dip in temperature at the onset of exercise is processed in the above-referenced Alt et al. pacemaker. More specifically, as described in the Alt et al. patent, the pacemaker employs several threshold-based criteria for interpreting a drop in a patient's central venous blood temperature as indicative of the commencement of exercise by a patient: (1) the absolute drop must exceed a certain minimum amount in the range of 0.12.degree. to 0.25.degree. C., (2) the time rate of change of the drop (.DELTA.T/.DELTA.t) must exceed a predetermined threshold slope, preferably in the range of from 0.12.degree. to 0.20.degree. C. per minute, and (3) the patient's heart rate must not exceed a predetermined threshold, preferably 85 beats per minute. At least the first two thresholds may be selected for a particular patient. The pacemaker's response to commencement of exercise is to abruptly increase stimulation rate by a step increase of selected magnitude, and to maintain that higher rate for a predetermined period of time followed by gradual reversion back toward the original rate. The magnitude of the drop and the magnitude of the rate of change of temperature are of no further significance. It is apparently only the relative magnitude of each, i.e., the magnitude relative to a threshold, as opposed to the absolute magnitude, which is considered useful by Alt et al. as a factor in setting pacing rate.
Significant progress has been made in temperature-based, rate modulation, but the known algorithms are still subject to improvement in the form of a more rapid and accurate algorithm more closely resembling the normal heart response to a variety of desirable and undesirable conditions experienced by pacemaker patients.